The long-term goal of this project is to understand the neural mechanisms involved in associative learning and specifically in the acquisition and expression of fear and anxiety in mammals. The project employs a model system approach using aversive Pavlovian conditioning in the rat. Presentation of an auditory stimulus that has been paired with an aversive event such as foot shock typically results in a constellation of behavioral and physiological responses which includes elevations in arterial blood pressure (ABP) and an attenuation of the organism's sensitivity to pain (hypoalgesia). This project will focus on a detailed analysis of the brain structures and connections that are essential for the learning and performance of hypoalgesic and cardiovascular conditional responses. These experiments will provide important new information about how biological processes occurring in the central nervous system give rise to psychological states like fear and anxiety. The project will also investigate the mechanisms and locations of plastic changes occurring within the nervous system during associative learning. Based on recent data from our laboratory, a functional neural system which includes the amygdala, periaqueductal gray (PAG) and rostral ventromedial medulla (RVM) is proposed as being critical for the expression of conditional fear-induced hypoalgesia (CHA). Rats will be prepared for intracranial microinjection and chronic measurement of ABP. After auditory fear conditioning animals will be tested for simultaneous changes in ABP and nociception in response to the aversive CS. The first set of experiments will compare the relative contribution of the central, lateral and basolateral nuclei of the amygdala and the PAG, RVM and lateral parabrachial region to response expression (performance) versus response acquisition (learning) by using selective reversible inactivation techniques. The second set of experiments will test our hypothesis that corticotropin releasing factor (CRF) plays an important neuromodulatory role in the synaptic connection between the amygdala and ventrolateral PAG during learning. The final set of studies will expand on our recent work which indicates that calcitonin gene-related peptide (CGRP) is released in the amygdala during conditioning and may be involved in plastic changes that occur during auditory fear conditioning.